1. Field of the Invention
The present invention relates generally to medical and/or biological testing and devices for performing same, and more particularly, to a method and apparatus for fluorescently staining immobilized nucleic acids. Fluorescent dyes are used which specifically bind to double-strand nucleic acids and/or which have detectably altered fluorescent properties when bound to such strands. Target nucleic acids are detected when hybridized to arrays of single-strand nucleic acid probes immobilized to solid substrates.
2. Description of the Related Art
Techniques for isolating and identifying genes and gene fragments and performing DNA sequencing are now in wide use. For example, in one technique, genomic DNA is digested with restriction enzymes, and then electrophoresed through agarose gels, and then blotted to GeneScreen (DuPont) utilizing standard procedures. Radiolabeled hybridization probes are prepared with the random hexamer labeling techniques described by Feinberg and Bogelstein (Analytical Biochemistry, 137:226-267,1984).
It is generally known how to use arrays of oligonucleotide probes to analyze target nucleic acids for specific nucleotide sequences by hybridization of the target to complementary probes in the array. The detection of hybridized sequences has typically involved pre-labeling the target nucleic acid with a fluorescent, radioactive or other detectable label in a time consuming step requiring expensive reagents.
The adsorption of non-hybridized, labeled nucleic acids to the array substrate can also result in high background signals which lower the sensitivity of hybridization detection.
Thus, a continuing need exists for methods and apparatuses that avoid the use of expensive reagents, while simplifying the overall procedures to require smaller samples and fewer processing steps.